SHR6390 Combined with Cabozantinib Inhibits Tumor Progression in theHepatocellular Carcinoma Mouse Model
Caiqi Liu, Jiaqi Shi, Binlin Lin, Meng Zhou, Dan Shan, Jianhua Nie, Yan Wang, Yanqiao Zhang, Peng Han, Tongsen Zheng
Abstract
Background: A novel CDK4/6 inhibitor SHR6390 has shown significant anti-tumor effects. However, its role in hepatocellular carcinoma (HCC) remains unknown. Objective: To explore the inhibitory effect of combination treatment with SHR6390 and cabozantinib in HCC, and its antitumor mechanism, so as to provide a more effective therapeutic strategy for HCC patients. Methods: We investigated SHR6390, monotherapy or combined with cabozantinib, by CCK8, wound healing, transwell, western blotting, immunohistochemistry and mouse model of a subcutaneous tumor. Results: Our results show that SHR6390 exhibited potent anti-proliferative activity against HCC in a dose-dependent manner. SHR6390 combined with cabozantinib exhibited more potent inhibition of cell viability, migration and invasion. In terms of potential mechanisms, we found that cabozantinib could lead to phosphorylation of Rb, which was reduced in SHR6390 and combined groups. SHR6390 monotherapy inhibited the growth of subcutaneous HCC tumors, besides, the combination treatment with SHR6390 and cabozantinib exerted synergistic anti-tumor activity in vivo. Conclusion: SHR6390 is effective against HCC, monotherapy or combined with cabozantinib.